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Between 5% and 15% of infants show symptoms suggestive of an adverse reaction to cow's milk protein (CMP). Prevalence estimates vary from 2% to 7.5% (1). This article is intended to illustrate the range of different presentations.

Terms such as food allergy, food intolerance and food hypersensitivity are often confused. Any adverse reaction to food is defined as food hypersensitivity, which can be either immune-mediated (allergy) or non-immune-mediated reactions (such as lactose intolerance). Food-allergic reactions may be broadly divided into immunoglobulin E- (IgE) mediated (immediate-onset) reactions and non IgE-mediated (delayed-onset) reactions (2).

Immune-mediated reactions to cow's milk

Cow's milk protein allergy (CMPA) is the most common food allergy in childhood (3). The incidence in infants is about 2-3% in developed countries but suggestive symptoms may be seen in around 5-15% of infants.

Allergy to cow's milk presents with a broad range of clinical symptoms and syndromes. In addition to the well-recognised immediate type IgE-mediated allergies – such as urticaria, angioedema and respiratory symptoms – a more diverse range of more delayed presentations such as eczema, gastrointestinal symptoms such as enteropathy, constipation, reflux and colic are increasingly being considered as part of the spectrum of milk allergy.

IgE-mediated reactions

41252471Immediate type 1 hypersensitivity reactions affect up to 8% of children, with cow's milk being the most common causative allergen. The vast majority of milk allergy presents within the first year of life.

Reactions usually occur within minutes of ingestion and range in severity from acute dermatological manifestations such as urticaria and angioedema to more severe, potentially life-threatening anaphylaxis.

Fatal allergic reactions to food are relatively rare in children and are most commonly caused by nuts, although fatal reactions to milk have occurred in young children. The presence of asthma, especially when not well controlled, has been shown to be a major risk factor for the occurrence of severe reactions.

Diagnosis of immediate cow's milk allergy relies both on history and IgE tests such as skin prick test or measurement of serum specific IgE antibody levels to cow's milk. In case of diagnostic doubt, a standardised double-blind placebo controlled food challenge (DBPCFC) is the gold-standard investigation.

Infants with immediate cow's milk allergy have usually outgrown the allergy during childhood, although recent data suggests only 20% will have done so by the age of four. Regular re-evaluation and allergy testing helps the clinician decide when the child has become tolerant, so that milk can be safely reintroduced. The risk of unpredictable IgE-mediated allergies dictates that reintroduction is attempted under controlled conditions.

Non-IgE-mediated reactions

CMP-induced proctocolitis

This is a disease of infancy usually presenting by two months with babies presenting with visible blood possibly mixed with mucus in the stool – but otherwise well and thriving. It is more common in, but not exclusive to, breast-fed babies whose mothers are ingesting cow's milk or soy protein.

The diagnosis is usually made on the basis of a response to the exclusion of cow's milk protein, either from the lactating mother's diet or by substitution by hypoallergenic milk formulae. Resolution is seen sooner than in IgE-mediated milk allergy with most infants tolerant by one to two years of age.

Cow's milk protein-induced enteropathy

Unlike those with CMP-induced proctocolitis, infants with enteropathy usually have protracted diarrhoea, which may result in malabsorption and failure to thrive. The natural history is similar to other forms of non-IgE mediated milk allergy, presenting in infancy and resolving by one to two years.

Food protein-induced enterocolitis syndrome

FPIES is a severe cell-mediated, gastrointestinal food hypersensitivity typically to cow's milk and soy and represents the severe end of the spectrum of milk allergy that affects only the gut.

It is characterised by severe protracted diarrhoea and vomiting, most commonly following ingestion of cow's milk or soy-based formula and can occur to a state of dehydration and cause shock in 20% of cases.

The cornerstone of management is careful exclusion under the supervision of a paediatric dietician.

Other immune-mediated reactions

Food sensitive eczema

41252472The association between eczema and food allergies has been well demonstrated. But attempts to show that dietary exclusions can objectively influence the course of atopic eczema remain unconvincing.

Attempts at meta-analysis of studies have been hampered by differences between the studies such as the age of patients, foods excluded and scoring systems for eczema severity. A review of 14 interventional studies suggests that dietary interventions, when guided by allergy testing, were efficacious, especially in younger children, under two years of age (4).

While skin prick testing and specific IgE blood testing may be helpful in detecting food allergy in children with eczema, around 10% of positive DBPCFC in these children were associated with being negative for both these tests. NICE guidance recommends a trial of hypoallergenic milk formula in children with moderate to severe, early-onset eczema, particularly if there are GI symptoms.

See the table below for how to find out if cow's milk is exacerbating eczema.

Allergic dysmotility

Gastro-oesophageal reflux is common in infancy and is caused by transient relaxation of the lower oesophageal sphincter. In some children, exclusion of cow's milk can markedly improve symptoms. Unfortunately, the non-IgE-mediated nature of this allergen-induced dysmotility means that traditionally allergy tests are unhelpful. A trial of milk exclusion should be considered in reflux when there is a strong family or personal history of allergy, failure to respond to first-line medications or suspicious history, such as worsening of symptoms on moving from breast to bottle feeding.

Allergic eosinophilic gastroenteropathies

This heterogeneous group of conditions includes eosinophilic oesophagitis (EO), eosinophilic gastroenteritis and eosinophilic gastroenterocolitis. Dietary exclusions have met with some success, alongside treatments such as steroids and leukotriene antagonists.

Other

Infantile colic has been shown to respond to extensively hydrolysed milk formulas in some studies (5) suggesting a possible role of food allergy. Infantile colic is poorly understood and although allergy may have a role it is unlikely to be more than one of a number of important influences.

The role of CMP as a cause of colonic dysmotility leading to constipation requires further investigation.

Conclusion

Allergic reactions to cow's milk range from mild proctocolitis to life-threatening anaphylaxis. Current management relies on allergen exclusion together with careful dietary supervision to ensure that nutrition is not compromised. Recognition and prompt treatment of reactions together with awareness of comorbidities also contribute to optimal management.

Dr Fox is one of the speakers at Practical Allergy for Primary Care a half day meeting designed for GPs who look after patients with allergic disease in their everyday practice. Interactive lectures and case based sessions will be led by GPs andspecialists. The meeting takes place at St Thomas' Hospital, London on the 5th May 2010 from 2.00pm to 5.00pm. Cost: GPs £25, Practice nurses/trainees £15.For further details of these as well as other events, visit www.allergyacademy.org or download the flyer (right)